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Novel Targeted CSU Therapies
The Next Chapter in CSU: How Novel Targeted Therapies Are Transforming Practice 

Released: March 11, 2026

Daniel Butler
Daniel Butler, MD
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Key Takeaways
  • CSU is a heterogeneous, mast cell–driven skin disease characterized by itchy wheals.
  • Novel targeted therapies like dupilumab, omalizumab, and remibrutinib are transforming the treatment landscape for CSU, allowing for a more personalized approach to patient care.
  • Clinical inertia will be a significant challenge for HCPs to overcome to effectively integrate these novel therapies into their practice. 

It is an exciting time for patients with chronic spontaneous urticaria (CSU) because the research is finally starting to unveil much more about its molecular mechanisms. This, in turn, will inform how we test, diagnose, and treat it—ultimately helping patients with CSU improve their quality of life. 

Going back to the basics, CSU is a heterogeneous, mast cell–driven skin disease with common pathways. Mast cells are finicky and have many influences. What happens in CSU is that mast cells get provoked and release irritants like histamine, cytokines, chemokines, cysteinyl leukotrienes, prostaglandins, and platelet-activating factors. This causes vasodilatation, vascular permeability, plasma extravasation, and nerve activation, which lead patients to develop 2 major symptoms. The first is wheals, which make up the famous morphology of this disease, and the second is itch, with CSU being one of the itchiest skin diseases people can have.

Novel Targeted Therapies for CSU
As mentioned, the latest research is starting to identify the many influences on mast cells that can cause CSU, and these upstream influences are what create a heterogeneous disease. This is important because it informs the development of targeted therapy that can impact this skin disease in a novel way.

Dupilumab is an interleukin (IL)-4/13 inhibitor, which is thought to downregulate the type 2 inflammation that can influence mast cells to cause itchy wheals. It is indicated to treat patients 12 years of age or older with CSU who remain symptomatic despite prior H1-antihistamine treatment. Another novel therapy is the oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib. BTK activation is part of the cellular signaling seen in CSU, which is what amplifies the autoimmune signal within mast cells. When these signals are blocked, there is a significant dampening of this autoimmune response. Like dupilumab, remibrutinib is indicated to treat adults with antihistamine-refractory CSU. Finally, omalizumab is an anti-IgE antibody that has been approved to treat CSU in symptomatic patients at least 12 years of age despite prior antihistamines for a while now. It is thought to improve patients’ disease by blocking free IgE from binding to mast cells and downregulating FcεRI expression on skin cells.

With the addition of these 3 targeted therapies to our more traditional options, the treatment landscape for CSU continues to expand. Historically, healthcare professionals (HCPs) were limited by symptom management with second-generation H1 antihistamines often needing escalation if there is no or inadequate response, and corticosteroids that cause significant immune suppression in order to treat patients. But now we can take a more personalized and targeted treatment approach that modifies the underlying mechanisms of CSU and improves patients’ quality of life.

Translating the Evidence Into Practice
As HCPs, we can translate these advances into patient care by meeting patients where they are and where they may have suffered before. This disease is often associated with patients who have suffered and been challenged for a long time. One of the most persistent misconceptions about CSU is that it is an allergic disorder. Although acute urticaria can be associated with an allergy or a sensitivity, it is very rare that CSU is related to a singular allergy or an environmental allergy.

This misconception has plagued patients for years, leading to significant over-testing. In the past, HCPs would order test after test, and everyone would ask about the root cause and why this was happening to them. At the end of the day, all that testing was generally for nothing. Maybe it provided a little indication of something else that could be going on, but regardless, it did not change the available treatment options that we had for patients with CSU.

Now we are entering an era where practice is moving away from all this testing. Instead, HCPs can better impact patients' quality of life by integrating novel therapies like remibrutinib, dupilumab, and omalizumab into their practice. All 3 targeted therapies were proven to be safe and effective through major clinical trials; now it is up to us, as dermatologists, to be open to using these agents in our daily practice.

For example, when I see patients with CSU, I certainly ask them about their symptoms and want to understand how much they are itching. The latter point is usually the driver in my determination of how seriously they need therapy. Occasionally, you will see someone who experiences urticaria flares every so often, but most patients with CSU are itchy for a significant amount of time. When you first see these patients, you should get them on second-generation H1 antihistamines as quickly as possible because that is the recommended first-line therapy. If patients break through after several weeks or months on antihistamines, I am quick to move them onto another, more targeted option.

A challenge in dermatology clinics is that not everyone carries omalizumab because HCPs are required to monitor patients in their office after administration due to anaphylaxis risk. Although that is an incredibly rare occurrence, particularly in patients with CSU, most dermatology HCPs will send patients out for this treatment. Now that we can use other targeted agents like remibrutinib and dupilumab, dermatology HCPs can easily administer these agents in their clinic, especially considering many of us have experience with using dupilumab in atopic dermatitis.

Your Thoughts
How often are you using targeted therapies like omalizumab, remibrutinib, or dupilumab in your patients with CSU? You can get involved in the conversation by answering the poll question and posting a comment below.

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How often are you using targeted therapies like omalizumab, remibrutinib, or dupilumab in your patients with CSU?

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